CD44 in myEloid cells is a major driver of liver inflammation and injury in alcohol-related liver disease.

Background And Aims: Alcohol-related liver disease (ALD) is one of the leading causes of severe liver disease with limited pharmacological treatments for alcohol-related steatohepatitis (ASH). CD44, a glycoprotein mainly expressed in immune cells, has been implicated in multiple inflammatory diseases but has never been studied in the ALD context. We therefore studied its contribution to ASH development in mice and its expression in ALD patients.

Rhythmic Exercises Before Basketball Training: A Study on Motor Skills, Static Balance, and Reaction Speed in School-Aged Children.

Racil, G, Padulo, J, Trabelsi, Y, Frizziero, A, Russo, L, and Migliaccio, GM. Rhythmic exercises before basketball training: A study on motor skills, static balance, and reaction speed in school-aged children. J Strength Cond Res 38(12): e761-e768, 2024-The aim of this study was to investigate the effects of combining rhythmic exercises with basketball training on the improvement of basic motor and physical skills in children.

Subclonal TP53 and KRAS variants combined with poor treatment response identify ultra-high-risk pediatric T-ALL patients.

Variations in the TP53 and KRAS genes indicate a particularly adverse prognosis in relapsed pediatric T-ALL. We hypothesized that these variations might be subclonally present at disease onset and contribute to relapse risk. To test this, we examined two cohorts of children diagnosed with T-ALL: one with 81 patients who relapsed and 79 matched non-relapsing controls, and another with 226 consecutive patients, 30 of whom relapsed.

l-Asparaginase Immobilized on Nanographene Oxide as an Efficient Nanobiocatalytic Tool for Asparagine Depletion in Leukemia Cells.

l-Asparaginase (l-ASNase) catalyzes the hydrolysis of l-asparagine, leading to its depletion and subsequent effects on the cellular proliferation and survival. In contrast to normal cells, malignant cells that lack asparagine synthase are extremely susceptible to asparagine deficiency. l-ASNase has been successfully employed in treating pediatric leukemias and non-Hodgkin lymphomas; however, its usage in adult patients and other types of cancer is limited due to significant side effects and drug resistance.

Design and Synthesis of Topoisomerases-Histone Deacetylase Dual Targeted Quinoline-Bridged Hydroxamates as Anticancer Agents.

The multifactorial nature of cancer requires treatment that involves simultaneous targeting of associated overexpressed proteins and cell signaling pathways, possibly leading to synergistic effects. Herein, we present a systematic study that involves the simultaneous inhibition of human topoisomerases (hTopos) and histone deacetylases (HDACs) by multitargeted quinoline-bridged hydroxamic acid derivatives. These compounds were rationally designed considering pharmacophoric features and catalytic sites of the cross-talk proteins, synthesized, and assessed for their anticancer potential.

Are Department Heads Ready for Change? Leveraging a Leadership Action Team to Advance Teaching Evaluation Practices.

Teaching evaluation at many institutions is insufficient to support, recognize, and reward effective teaching. We developed a long-term intervention to support science, technology, engineering, and mathematics (STEM) department heads in advancing teaching evaluation practices. We describe the intervention and systematically investigate its impact on departmental practices within a research-intensive university.

Naturally occurring variation in a cytochrome P450 modifies thiabendazole responses independently of beta-tubulin.

Widespread anthelmintic resistance has complicated the management of parasitic nematodes. Resistance to the benzimidazole (BZ) drug class is nearly ubiquitous in many species and is associated with mutations in beta-tubulin genes. However, mutations in beta-tubulin alone do not fully explain all BZ resistance.

Mechanisms for dysregulation of excitatory-inhibitory balance underlying allodynia in dorsal horn neural subcircuits.

Chronic pain is a wide-spread condition that is debilitating and expensive to manage, costing the United States alone around $600 billion in 2010. In a common symptom of chronic pain called allodynia, non-painful stimuli produce painful responses with highly variable presentations across individuals. While the specific mechanisms remain unclear, allodynia is hypothesized to be caused by the dysregulation of excitatory-inhibitory (E-I) balance in pain-processing neural circuitry in the dorsal horn of the spinal cord.

The chromatin remodeler ADNP regulates neurodevelopmental disorder risk genes and neocortical neurogenesis.

Although chromatin remodelers are among the most important risk genes associated with neurodevelopmental disorders (NDDs), the roles of these complexes during brain development are in many cases unclear. Here, we focused on the recently discovered ChAHP chromatin remodeling complex. The zinc finger and homeodomain transcription factor ADNP is a core subunit of this complex, and de novo mutations lead to intellectual disability and autism spectrum disorder.

The mosquito evolves two types of prophenoloxidases with diversified functions.

Insect phenoloxidase, presented as an inactive precursor prophenoloxidase (PPO) in hemolymph, catalyzes melanin formation, which is involved in wound healing, pathogen killing, reversible oxygen collection during insect respiration, and cuticle and eggshell formation. Mosquitoes possess 9 to 16 PPO members across different genera, a number that is more than that found in other dipteran insects. However, the reasons for the redundancy of these PPOs and whether they have distinct biochemical properties and physiological functions remain unclear.

A twofold perspective on the quality of research publications: The use of ICTs and research activity models.

Previous studies have highlighted the inherent subjectivity, complexity, and challenges associated with research quality leading to fragmented findings. We identified determinants of research publication quality in terms of research activities and the use of information and communication technologies by employing an interdisciplinary approach. We conducted web-based surveys among academic scientists and applied machine learning techniques to model behaviors during and after the COVID-19 pandemic.

Unravelling the transcriptomic dynamics of Hyphopichia pseudoburtonii in co-culture with Botrytis cinerea.

Hyphopichia pseudoburtonii, is emerging as a potential biocontrol agent against various phytopathogens. These traits have been attributed to the production of various antifungal compounds in the presence of target pathogens. However, the broad molecular mechanisms involved in the antifungal activity are not yet understood.

Cognitive impairment caused by compromised hepatic ketogenesis is prevented by endurance exercise.

Extensive research has demonstrated endurance exercise to be neuroprotective. Whether these neuroprotective benefits are mediated, in part, by hepatic ketone production remains unclear. To investigate the role of hepatic ketone production on brain health during exercise, healthy 6-month-old female rats underwent viral knockdown of the rate-limiting enzyme in the liver that catalyses the first reaction in ketogenesis: 3-hydroxymethylglutaryl-CoA synthase 2 (HMGCS2).

mTORC1 regulates the pyrimidine salvage pathway by controlling UCK2 turnover via the CTLH-WDR26 E3 ligase.

One critical aspect of cell proliferation is increased nucleotide synthesis, including pyrimidines. Pyrimidines are synthesized through de novo and salvage pathways. Prior studies established that the mammalian target of rapamycin complex 1 (mTORC1) promotes pyrimidine synthesis by activating the de novo pathway for cell proliferation.

Standard: Human gastric organoids.

Organoid technology provides a transformative approach to understand human physiology and pathology, offering valuable insights for scientific research and therapeutic development. Human gastric organoids, in particular, have gained significant interest for applications in disease modeling, drug discovery, and studies of tissue regeneration and homeostasis. However, the lack of standardized quality control has limited their extensive clinical applications.

TeMac™ ameliorates memory impairment and cholinergic dysfunction in rats induced by scopolamine.

Alzheimer's disease (AD) is associated with cognitive impairments which are linked to a deficit in cholinergic function. The objective of this study was to evaluate the ability of TeMac™ to prevent memory impairment in scopolamine-rats model of Alzheimer's disease and by in silico approaches to identify molecules in TeMac™ inhibiting acetylcholinesterase. The cholinergic cognitive dysfunction was induced by intraperitoneal injection of scopolamine (1 mg/kg daily) in male Wistar rats for seven consecutive days.

MALDI-MSI: A potential game changer in forensic sciences.

Matrix-assisted laser Desorption/Ionization Mass Spectrometry Imaging (MALDI MSI) is an analytical technique used for the spatial mapping of drugs, explosives, and organic samples, making it a game-changer in Forensic examination. It detects a wide range of biomolecules in their native state without specific tags, antibodies, labels, and dyes. This review aims to highlight the advancement of MALDI-MSI over time and its impact on Forensic Science due to high-resolution molecular imaging.

Epigenetics in the modern era of crop improvements.

Epigenetic mechanisms are integral to plant growth, development, and adaptation to environmental stimuli. Over the past two decades, our comprehension of these complex regulatory processes has expanded remarkably, producing a substantial body of knowledge on both locus-specific mechanisms and genome-wide regulatory patterns. Studies initially grounded in the model plant Arabidopsis have been broadened to encompass a diverse array of crop species, revealing the multifaceted roles of epigenetics in physiological and agronomic traits.

Peficitinib suppresses diffuse-type tenosynovial giant cell tumor by targeting TYK2 and JAK/STAT signaling.

Diffuse-type tenosynovial giant cell tumor (dTGCT) is a destructive but rare benign proliferative synovial neoplasm. Although surgery is currently the main treatment modality for dTGCT, the recurrence risk is up to 50%. Therefore, there is a great need for effective drugs against dTGCT with minor side effects.

Polyphenols as Wnt/β-catenin pathway modulators: A promising strategy in clinical neurodegeneration.

Polyphenols, a diverse group of naturally occurring compounds found in plants, have garnered significant attention for their potential therapeutic properties in treating neurodegenerative diseases (NDs). The Wnt/β-catenin (WβC) signaling pathway, a crucial player in neurogenesis, neuronal survival, and synaptic plasticity, is involved in several cellular mechanisms related to NDs. Dysregulation of this pathway is a hallmark in the development of various NDs.

Stereospecific Resistance to N2-Acyl Tetrahydro-β-carboline Antimalarials Is Mediated by a PfMDR1 Mutation That Confers Collateral Drug Sensitivity.

Half the world's population is at risk of developing a malaria infection, which is caused by parasites of the genus . Currently, resistance has been identified to all clinically available antimalarials, highlighting an urgent need to develop novel compounds and better understand common mechanisms of resistance. We previously identified a novel tetrahydro-β-carboline compound, PRC1590, which potently kills the malaria parasite.

Detection and quantification of ergothioneine in human serum using surface enhanced Raman scattering (SERS).

Ergothioneine (ERG) is a natural sulfur-containing amino acid found in many organisms, including humans. It accumulates at high concentrations in red blood cells and is distributed to various organs, including the brain. ERG has numerous health benefits and antioxidant capabilities, and it has been linked to various human physiological processes, such as anti-inflammatory, neuroprotective, and anti-aging effects.

Modeling the navigating forces behind BSA aggregation in a microfluidic chip.

Microfluidic chips are powerful tools for investigating numerous variables including chemical and physical parameters on protein aggregation. This study investigated the aggregation of bovine serum albumin (BSA) in two different systems: a vial-based static system and a microfluidic chip-based dynamic system in which BSA aggregation was induced successfully. BSA aggregation induced in a microfluidic chip on a timescale of seconds enabled a dynamic investigation of the forces driving the aggregation process.

Emerging themes in microbial stress response and mechanistic insights: key findings from the fall 2024 ASM Theobald Smith Society meeting.

The annual fall meeting for the Theobald Smith Society was held in November 2024 on the campus of Rutgers University-New Brunswick. Eighty-six branch members from across New Jersey attended the meeting, composed of undergraduate, graduate, and postdoctoral trainees, faculty members, and government and industry professionals. This report highlights the breadth and diversity of research conducted by American Society for Microbiology members in the Theobald Smith Society and celebrates their groundbreaking discoveries.